Combating unhealthy weight gain is a major public health and clinical management issue. The extent of research into the etiology and pathophysiology of obesityhas produced a wealth of evidence regarding the contributing factors. While aspects of the environment are ‘obesogenic’,weight gain is not inevitable for every individual. What then explains potentially unhealthy weight gain inindividuals living within an environment where others remainlean? In this paper we explore the biological compensationthat acts in response to a reduced energy intake by reducing energy needs, in order to defend against weight loss. We then examine the evidence that there is only a weakbiological compensation to surplus energy supply, and thatthis allows behavior to drive weight gain. The extent to which biology impacts behavior is also considered. and has frequently been attributed to a lack of daily physical activity, and to the abundance of inexpensive, palatable and energy-dense foods . There is no question that the environment plays a critical role in determining whether or not an individual is in a situation where they have the possibility of being in energy surplus, or positive energy balance [3–5].We are able to view first-hand, or for most of us via our television screens, the consequences that befall communities such as those in Sub-Saharan Africa which experience continued famine. Without adequate energy intake, body weight cannot be maintained, let alone gained. Therefore, we can acknowledge the credence in the First Law of Thermodynamics, and note that for energy to be stored in the body tissues and for body weight to be gained; we must have an energy surplus to be stored. So moving beyond this basic tenet, what factors most strongly contribute to weight gain in individuals in the environmental circumstance where there is the opportunity to be in positive energy balance?